There is abundant evidence from our laboratory, as well as others, that the traffic patterns of specifically reactive circulating lymphocytes can be manipulated by antigenic challenge. We now have substantial evidence in mice that the intra-bone marrow traffic of circulating lymphocytes with specific graft versus host (GVH) reactivity can be selectively reduced by challenging them in their four foot pads with alloantigen plus the adjuvant C. parvum (alloantigen-adjuvant regimen). Furthermore, we have equally substantial evidence that this alloantigen-adjuvant regimen can be used on bone marrow donors to successfully transplant their marrow across the strong H-2 barrier in mice. The immediate objectives of this proposal are: (1) To further substantiate the ability of our alloantigen-adjuvant regimen to delete GVH reactivity from allogeneic marrow by using it in murine donor:recipient strain combinations other than that of the C57BL/6J to A/J, and C57BL to AKR/J combinations, with which we have already been successful, (2) To evaluate the use of allogeneic marrow depleted of specific GVH reactivity by our alloantigen-adjuvant regimen in combination with chemoradiotherapy to prevent the development of or "cure" of the leukemia-lymphomas that arise spontaneously in AKR and SJL mice; (3) To determine if our alloantigen-adjuvant regimen can be used to successfully transplant bone marrow across the major histocompatibility complex (DL-A) in selectively bred beagles and outbred mongrel dogs. The long-term objectives of this proposal are: to use our alloantigen-adjuvant regimen to transplant marrow across the major histocompatibility complex (HL-A) in humans. Although our principal interest will be to use allogeneic marrow (freed of specific GVH reactivity) as part of a combined immunotherapeutic and chemoradiotherapeutic regimen to treat selected patients with leukemia or lymphoma, it might also be useful to treat patients with a variety of non-neoplastic diseases such as aplastic anemia, genetic blood diseases, immunodeficiency diseases and victims of lethal doses of ionizing radiation.